title: Effects of adrenomedullin and vascular endothelial growth factor on ischemia/reperfusion injury in skeletal muscle in rats.
abstract: BACKGROUND
  In this study we investigated the effects of adrenomedullin (AM) and vascular endothelial growth factor (VEGF) on skeletal muscle ischemia/reperfusion (I/R) injury in a rat model.
  
  
  METHODS
  Thirty-six Wistar rats were randomized into six groups (n = 6). Laparotomy was performed in all groups under general anesthesia. Nothing else was done in Group S (Sham). The Group I/R underwent I/R performed by clamping and declamping of the infrarenal abdominal aorta for 120 min, respectively. Group VEGF and Group AM received intravenous infusion of VEGF (0.8 μg/kg) or AM (12 μg/kg) respectively, without I/R. Group I/R + VEGF and Group I/R + AM received intravenous infusion of VEGF (0.8 μg/kg) or AM (12 μg/kg) immediately after 2 h period of ischemia, respectively. At the end of reperfusion period, skeletal muscle samples of lower extremity were taken from all groups for biochemical and histopathologic examinations.
  
  
  RESULTS
  Tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), and hypoxia inducible factor 1 alpha (HIF 1α) were found to be significantly higher in Group I/R than the levels in Group S (P < 0.05). Tissue levels of MDA, SOD, NO, and HIF 1α were significantly lower in Group I/R + AM compared with the levels in Group I/R (P < 0.05). In Group I/R + VEGF, tissue levels of MDA and NO were significantly lower than the levels in Group I/R (P < 0.05). No statistically significant difference was found in the tissue levels of catalase among the groups. Histologic examination revealed a larger central muscular necrosis than the peripheral necrosis, red blood cells in the lumens of capillary vessels, and a stronger atrophy and elliptical or round shape in muscle fibers in Group I/R. Terminal deoxynucleotidyl transferase mediated dUPT nick end labeling (TUNEL)-positive cell count was significantly lower in groups I/R + AM and I/R + VEGF than Group I/R (P < 0.0001, P < 0.0001, respectively).
  
  
  CONCLUSIONS
  These results indicate that AM and VEGF have protective effects on I/R injury in skeletal muscle in a rat model.
authors.affiliation: Department of Cardiovascular Surgery, Faculty of Medicine, Gazi University, Ankara, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kirisci
authors.forename: Gursel Levent
authors.initials: GL
authors.lastname: Oktar
authors.forename: Candan
authors.initials: C
authors.lastname: Ozogul
authors.forename: Eser Oz
authors.initials: EO
authors.lastname: Oyar
authors.forename: Seda Nur
authors.initials: SN
authors.lastname: Akyol
authors.forename: Canan Yilmaz
authors.initials: CY
authors.lastname: Demirtas
authors.forename: Mustafa
authors.initials: M
authors.lastname: Arslan
mesh_terms: D053607:Adrenomedullin / Q000494:pharmacology*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D004195:Disease Models, Animal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D053607:Adrenomedullin; D009569:Nitric Oxide; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase
keywords: Adrenomedullin; Histopathology; Ischemia/reperfusion; Rat; Skeletal muscle; VEGF